Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Stereodivergent synthesis of the C61–C74 and C69–C83 fragments of symbiodinolide elucidated the relative configuration of its C61–C83 fragment.

DOI： 10.1039/d3ob01420g

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Hybridization of monoterpene and furan structural scaffolds increased antifouling activity.

DOI： 10.1039/d2ob02203f

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.orglett.2c03263

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

Xylemin (6) and its designed structural analogues 18-23, N-(4-aminobutyl)alkylamines, were synthesized by 2-nitrobenzenesulfonamide (Ns) strategy. Investigation of the improved synthesis of 20-23 resulted in the development of one-step synthesis of these analogues from the commercially available corresponding ketones. Biological assessment of the synthetic molecules elucidated that xylemin (6) and the analogue N-(4-aminobutyl)cyclopentylamine (21) promoted the expression level of thermospermine synthase ACAULIS5 (ACL5) and enhanced xylem formation. In addition, xylemin (6) was found to significantly promote lateral root formation, whereas xylemin analogues 18-23 including 21 did not. These results indicate that the analogue 21 has the potential as a novel inhibitor of thermospermine synthesis to work specifically in xylem differentiation.

DOI： 10.1002/ejoc.202000322

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：The Society of Synthetic Organic Chemistry, Japan  

DOI： 10.5059/yukigoseikyokaishi.77.1190

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

A stereoselective synthesis of the macrolactone core of neopeltolide is described. The tetrahydropyran moiety was constructed via the intramolecular allylation of an alpha-acetoxy ether. A late-stage macrolactonization provided a known synthetic intermediate of neopeltolide. (C) 2018 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2018.12.066

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：The Japan Institute of Heterocyclic Chemistry  

DOI： 10.3987/com-18-s(f)44

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：The Japan Institute of Heterocyclic Chemistry  

DOI： 10.3987/com-18-s(f)8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

A stereoselective formal total synthesis of enigmazole A, a marine macrolide isolated from Cinachyrella enigmatica, is described. Lewis acid mediated intramolecular allylation of an alpha-acetoxy ether, prepared from alcohol and carboxylic acid fragments was carried out to construct the methylene THP ring with high stereoselectivity. The late-stage macrolactonization of the corresponding seco-acid provided a known synthetic intermediate of enigmazole A. (C) 2018 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2018.11.017

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of genus Sarcophyton. Unified total synthesis of sarcophytonolides C, E, F, G, H, and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS- or SmI2-mediated fragment coupling, alkoxycarbonylallylation, macrolactonization, and transannular ring closing metathesis. These total syntheses led to the absolute configurational confirmation of sarcophytonolide H, elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide J and isosarcophytonolide D. We also evaluated the antifouling activity and toxicity of the synthetic sarcophytonolides H and J and their analogues as well as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic intermediates.

DOI： 10.1021/acs.joc.8b01634

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Chemical Society of Japan  

An improved synthesis of the A-E ring segment of ciguatoxin CTX3C is described. The E ring segment was synthesized by the intramolecular reaction of allylic stannane and aldehyde with high stereoselectivity. Construction of the A-E ring framework was performed by using the intramolecular allylation of alpha-acetoxy ether followed by ring-closing metathesis.

DOI： 10.1246/bcsj.20170390

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.tetlet.2018.02.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

A convergent total synthesis of (-)-dactylolide is described. Constructing the 2,6-disubstituted exo-methylene THP moiety was achieved by the intramolecular allylation of alpha-acetoxy ether. The cyclization precursor was prepared from two segments, an alcohol and carboxylic acid derivatives, by esterification followed by reductive acetylation. (C) 2018 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2018.01.034

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Institute of Heterocyclic Chemistry  

A stereoselective total synthesis of rhoiptelol B, a diarylheptanoid isolated from the fruits of Rhoiptelea chiliantha, is described. The tetrahydropyran ring was constructed via an intramolecular allylation methodology.

DOI： 10.3987/com-18-s(t)57

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

The first total synthesis of two possible diastereomers of natural 6-chlorotetrahydrofuran acetogenin 1 has been achieved. The synthetic route features 5-exo-tet cyclization, Z selective Wittig reaction and Julia olefination for the construction of conjugated diene and enyne moieties, and stereoselective chlorination. Comparison of their H-1 and (CNMR)-C-13 data and specific rotation with those of the natural product elucidated the absolute configuration of natural (-)-6-chlorotetrahydrofuran acetogenin 1.

DOI： 10.1002/chem.201704514

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Hybrid molecules consisting of geraniol and butenolide were designed and synthesized by the late-stage divergent strategy. In the synthetic route, ring-closing metathesis was utilized for the construction of a butenolide moiety. A biological evaluation of the eight synthetic hybrid compounds revealed that these molecules exhibit antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC50 values of 0.30-1.31 mu g mL(-1). These results show that hybridization of the geraniol and butenolide structural motifs resulted in the enhancement of the antifouling activity.

DOI： 10.1039/c7ob01160a

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The first total syntheses of sarcophytonolide H and the originally proposed and correct structures of isosarcophytonolide D have been achieved via transannular ring-closing metathesis (RCM). These total syntheses culminated in the stereostructural confirmation of sarcophytonolide H and the reassignment of isosarcophytonolide D, respectively. The antifouling activity of the synthetic sarcophytonolide H and its analogues was also evaluated.

DOI： 10.1021/acs.orglett.6b00737

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/chem.201504863

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The xylem conducts water and minerals from the root to the shoot and provides mechanical strength to the plant body. The vascular precursor cells of the procambium differentiate to form continuous vascular strands, from which xylem and phloem cells are generated in the proper spatiotemporal pattern. Procambium formation and xylem differentiation are directed by auxin. In angiosperms, thermospermine, a structural isomer of spermine, suppresses xylem differentiation by limiting auxin signalling. However, the process of auxin-inducible xylem differentiation has not been fully elucidated and remains difficult to manipulate. Here, we found that an antagonist of spermidine can act as an inhibitor of thermospermine biosynthesis and results in excessive xylem differentiation, which is a phenocopy of a thermospermine-deficient mutant acaulis5 in Arabidopsis thaliana. We named this compound xylemin owing to its xylem-inducing effect. Application of a combination of xylemin and thermospermine to wild-type seedlings negates the effect of xylemin, whereas co-treatment with xylemin and a synthetic proauxin, which undergoes hydrolysis to release active auxin, has a synergistic inductive effect on xylem differentiation. Thus, xylemin may serve as a useful transformative chemical tool not only for the study of thermospermine function in various plant species but also for the control of xylem induction and woody biomass production.

DOI： 10.1038/srep21487

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

We have synthesized eight possible diastereoisomers 3a-h of the C79-C97 fragment of symbiodinolide (1) in a stereodivergent manner by utilizing a dithiane addition to the aldehyde as a key step. Comparison of the (CNMR)-C-13 chemical shifts of the natural product 1 and the synthetic products 3a-h indicated that the relative stereostructure of this fragment in symbiodinolide (1) is that represented in 3a or f. We have stereodivergently synthesized eight possible diastereoisomers of the C94-C104 fragment 4a-h, and we have compared their (CNMR)-C-13 chemical shifts with those of the natural product, which established the relative stereochemistry of this fragment to be that described in diastereoisomers 4a or e. By combining the stereostructural outcomes of the C79-C97 and C94-C104 fragments, we have proposed four candidate compounds of the C79-C104 fragment 2a-d. We also synthesized diastereoisomers 2a and b (2a in the preceding article; Chem. Eur. J. 2015, DOI: 10.1002/chem.201503880) by a Julia-Kocienski olefination and diastereoisomers 2c and d by a Wittig reaction. By comparing the (CNMR)-C-13 chemical shifts of natural symbiodinolide (1) with those of the synthetic products 2a-d, we have reassigned the stereostructure of the C79-C104 fragment of natural product 1 to be that depicted in diastereoisomer 2b.

DOI： 10.1002/chem.201503881

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

Stereoselective and streamlined synthesis of the proposed C79-C104 fragment 2 of symbiodinolide (1), a polyol marine natural product with a molecular weight of 2860, was achieved. In the synthetic route, the proposed C79-C104 fragment 2 was synthesized by utilizing a Julia-Kocienski olefination and subsequent Sharpless asymmetric dihydroxylation as key transformations in a convergent manner. Detailed comparison of the (CNMR)-C-13 chemical shifts between the natural product and the synthetic C79-C104 fragment 2 revealed that the stereostructure at the C91-C99 carbon chain moiety of symbiodinolide (1) should be reinvestigated.

DOI： 10.1002/chem.201503880

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Convergent synthesis of the EFGH ring segment of ciguatoxin CTX3C was investigated by using the intramolecular allylation of an alpha-chloroacetoxy ether and/or O,S-acetal, and subsequent ring-closing metathesis. A new method for the preparation of gamma-alkoxyallylstannane is also described. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2015.04.106

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Four possible diastereomers of the C1-C13 fragment of symbiodinolide, which were proposed by the stereostructural analysis of the degraded product, were synthesized in a stereodivergent and stereoselective manner. The key transformations were aldol reaction of methyl acetoacetate with the aldehyde, diastereoselective reduction of the resulting beta-hydroxy ketone, and the stereoinversion at the C6 position. Comparison of the H-1 NMR data between the four synthetic products and the degraded product revealed the relative stereostructure of the C1-C13 fragment of symbiodinolide.

DOI： 10.1021/acs.joc.5b00027

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

An enantio- and stereoselective synthesis of the C1-C7 fragment of enigmazole A is described. The three asymmetric centers of the molecule were constructed efficiently by using Evans chiral auxiliary protocol.

DOI： 10.3987/COM-13-12905

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The improved synthesis of the A-E ring segment of ciguatoxin CTX3C was performed via a highly convergent approach based on intramolecular allylation-RCM methodology.

DOI： 10.3987/COM-13-S(S)106

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Language：Japanese   Publisher：Society of Synthetic Organic Chemistry  

Symbiodinolide is a polyol marine natural product isolated from dinoflagellate Symbiodinium sp. This natural product exhibits voltage-dependent N-type Ca2+ channel-opening activity at 7 nM and COX-1 inhibition activity at 2 μM. The planar structure of symbiodinolide was elucidated by the detailed 2D NMR analysis. However, the huge and complex molecular structure of this molecule featuring a molecular weight of 2,860 and the presence of 61 chiral centers has hampered the complete stereochemical determination. Herein, we report our synthetic study of symbiodinolide toward the structural elucidation.

DOI： 10.5059/yukigoseikyokaishi.72.2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BEILSTEIN-INSTITUT  

Symbiodinolide is a polyol marine natural product with a molecular weight of 2860. Herein, a streamlined synthesis of the C79-C97 fragment of symbiodinolide is described. In the synthetic route, a spiroacetalization, a Julia-Kocienski olefination, and a Sharpless asymmetric dihydroxylation were utilized as the key transformations.

DOI： 10.3762/bjoc.9.228

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Language：English   Publishing type：Research paper (scientific journal)  

A highly stereoselective and stereodivergent synthesis of two possible diastereomers of (-)-gummiferol was achieved, wherein the stepwise epoxidation and Cadiot-Chodkiewicz reaction were utilized for the construction of the diepoxide moiety and triacetylene part, respectively. Detailed comparison of their 1H and 13C NMR data and specific rotation with those of the natural product unambiguously elucidated the absolute stereostructure of gummiferol. In addition, the cytotoxic activity of the synthesized gummiferol, its stereoisomers, and its truncated analogues was evaluated, which clearly indicates that (1) the absolute configuration of the diepoxide moiety has little influence on the cytotoxic activity against human cancer cells and (2) the triacetylene unit is the crucial structural element required for exerting the cytotoxic activity. © 2013 American Chemical Society.

DOI： 10.1021/jo302665c

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Stereoselective and parallel total syntheses of two possible diastereomers of (+)-sarcophytonolide C have been accomplished. Macrolactonization and transannular ring-closing metathesis (RCM) were the key transformations. Detailed comparisons of their H-1 and C-13 NMR data and specific rotation with those of the natural product allowed the absolute configuration of (+)-sarcophytonolide C to be determined.

DOI： 10.1021/ol400157s

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Stereocontrolled synthesis of the E ring segment of ciguatoxin CTX3C was performed via the Negishi coupling of cyclic ketene acetal triflates. Transformation of 8-membered lactones to the corresponding ketene acetal triflates was found to be affected by the protective groups of the substrates.

DOI： 10.3987/COM-12-S(N)117

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Stereoselective synthesis of the C94-C104 fragment of symbiodinolide which is a polyol marine natural product with a molecular weight of 2860 has been accomplished. The synthetic route features Achmatowicz rearrangement and RuO4-catalyzed dihydroxylation for the construction of the tetrahydropyran moiety and the dithiane addition to the aldehyde for the introduction of the side chain. (c) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2012.06.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

A convergent synthesis of the right-hand fragment of ciguatoxin CTX3C was investigated. The first and second generation stereocontrolled syntheses of the LM ring fragment were achieved via spiroacetalization as a key step, respectively. The polyether framework of the HIJKLM ring fragment was constructed in a convergent manner by using intramolecular allylation, ring-closing metathesis, and stereoselective hydrogenation to form the 36-methyl substituent as the key transformations. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2012.01.071

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The HIJKLM ring system of ciguatozin CTX3C was synthesized in a convergent manner. The key steps were a conjugate addition/alkylation sequence, spiroacetalization, intramolecular allylation, ring-closing metathesis, and hydrogenation to form the 36-alpha-methyl substituent.

DOI： 10.1021/ol2019136

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Stereoselective synthesis of two possible diastereomers of (-)-gummiferol was accomplished by the stepwise epoxidation and Cadiot-Chodkiewicz reaction as the key transformations. Detailed comparison of their (1)H and (13)C NMR data and specific rotation with those of the natural product led to the absolute structural elucidation of (-)-gummiferol.

DOI： 10.1021/ol201301b

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The C14-C24 fragment of symbiodinolide possessing the 17R/18R/21R absolute configuration, which was obtained as one of the degraded products of symbiodinolide, and its diastereomer possessing the 17R/18S/21R absolute stereochemistry were synthesized stereoselectively from cis-2-butene-1,4-diol, respectively. The detailed comparison of the synthetic products with the degraded product in the spectroscopic data confirmed unambiguously that the stereostructure of the C14-C24 fragment was 17R, 18R, and 21R. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2010.07.045

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

A convenient method for the stereoselective construction of angular methyl group of fuzed cyclic ethers is described. Reactions of mixed thioacetals with Me(2)Zn/Zn(OTO)(2) afforded the corresponding methylated products in good yields. Various protective groups such as MOM ether, benzylidene acetal, TBS ether, and pivaloyl group were stable under the reaction conditions. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2010.05.109

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The convergent total synthesis of brevenal, a non-toxic brevetoxin antagonist, has been achieved. The ABC ring segment and the E ring precursor were connected by the intramolecular allylation followed by ring-closing metathesis to furnish the pentacyclic ether compound. An alternative route to the key synthetic intermediate, a pentacyclic ether core, was also examined. The right- and left-hand side chains were introduced by Wittig and Horner-Wadsworth-Emmons reactions, respectively, to furnish brevenal (1). (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2010.05.069

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Symbiodinolide is a polyol macrolide isolated from the marine dinoflagellate Symbiodinium sp. in 2007. The C14-C24 fragment of symbiodinolide possessing the 17R/18R/21R absolute configuration, which was obtained as one of the degraded products of symbiodinolide, was synthesized stereoselectively from cis-2-butene-1,4-diol. The detailed comparison of the synthetic product with the degraded product in the spectroscopic data confirmed that the stereostructure of the C14-C24 fragment was 17R, 18R, and 21R. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2010.03.014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Cross-metathesis of methyl ester which was prepared from symbiodinolide with ethylene was performed to give the C33-C42 degraded fragment. This fragment was estimated to be (36S,40S)-diol by the modified Mosher method. Stereoselective synthesis of the (36S,40S)-diol and its diastereomer (36R,40S)-diol was achieved from L-aspartic acid. Synthetic bis-(S)- and (R)-MTPA esters which were derivatized from the (36S,40S)-diol exhibited spectroscopic data identical with those of bis-(S)- and (R)-MTPA esters derived from the degraded product. Thus, the absolute stereochemistry of the C33-C42 fragment was elucidated to be (36S,40S). (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2009.07.019

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The degradation product C14-C23 2 was obtained using ethenolysis with the 2nd-generation Hoveyda-Grubbs catalyst from 62-membered lactone in symbiodinolide (1). The absolute configurations of three chiral centers in fragment 2 were assigned as 17R, 18R, and 21R by a combination of J-based configuration analysis and the Mosher-Riguera method. (c) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2009.07.014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Stereoselective synthesis of the C1'-C25' fragment of symbiodinolide, which was obtained as a degraded product from symbiodinolide by alkaline hydrolysis, has been accomplished. The synthetic route features Kotsuki coupling and Julia-Kocienski olefination in the introduction of the side chains. This enantio-and stereoselective synthesis has established the absolute configuration of the C1'-C25' fragment.

DOI： 10.1021/jo901162v

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

A convergent synthesis of the A-E ring segment of ciguatoxin CTX3C was achieved via the intramolecular allylation of an alpha-chloroacetoxy ether and subsequent ring-closing metathesis. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2009.07.037

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

A useful method for the selective cleavage of primary MPM ethers by using TMSI/Et3N is described. Other protective groups such as secondary MPM ethers, silyl ethers, and benzylidene acetal were stable under the reaction conditions. (C) 2009 Elsevier Ltd. Ail rights reserved.

DOI： 10.1016/j.tetlet.2009.05.084

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Stereoselective synthesis of the C23-C34 fragment of symbiodinolide, which possesses the originally proposed stereochemistry, and its diastercomers was achieved in 19 steps from L-aspartic acid, respectively. Comparison of spectroscopic data of the synthetic products with those of the degraded product of symbiodinolide led to a structural revision of the C23-C34 fragment.

DOI： 10.1021/jo900546k

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A total synthesis of brevenal is described. The pentacyclic ether core was constructed by the intramolecular allylation of alpha-acetoxy ether and subsequent ring-closing metathesis. Both of the diene side chains were introduced by Wittig olefination and a Horner-Wadsworth-Emmons reaction, respectively, in a highly stereoselective manner.

DOI： 10.1021/ol900769d

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Synibiodinolide (1) is a polyol macrolide with a molecular weight of 2859 mu. As one of the degradation reactions, cross-metathesis of 2, which is a methyl ester of 1, with ethylene was performed to give the C33-C42 degraded fragment 4. The absolute configuration of 4 was estimated to be (36S,40S) by Mosher method. Stereoselective synthesis of 4 was achieved in 14 steps from L-aspartic acid. Synthetic bis-(S)-and (R)-MTPA esters exhibited the spectroscopic data identical with those of bis-(S)- and (R)-MTPA esters derived from the degraded fragment 4. Thus, the absolute stereochemistry of 4 was elucidated to be (36S,40S). (C) 2009 Published by Elsevier Ltd.

DOI： 10.1016/j.tetlet.2008.11.056

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The transannular Diels-Alder (TADA) reaction was applied to the synthesis of the CDE ring system of nakiterpiosin (1). TADA product 28 is a key intermediate toward the total synthesis of 1.

DOI： 10.3987/COM-08-S(F)26

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The stereoselective synthesis of the C79-C96 fragment of symbiodinolide is described in which the spiroacetalization and Kotsuki coupling are the key steps. (c) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2008.05.078

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Synthesis of the AB ring segments of ciguatoxin is described. The present synthesis includes a Lewis acid mediated cyclization of allylstannane with aldehyde, cross-metathesis reaction introducing the side chain, and Grieco-Nishizawa dehydration on the A ring. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2008.03.145

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Kansuinine A, isolated from the plant Euphorbia kansui Liou, is one of a series of jatrophane diterpenes that have novel structural features, which include contiguous stereocenters, a highly oxygenated carbon framework, and a tricyclic ring system. We describe here a short and concise synthesis of the cyclopentane segment of kansuinine A via SmI2-mediated cyclization of delta-iodoester as a key construction method. (c) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2007.06.046

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The transarmular Diels-Alder (TADA) reaction was applied to the synthesis of the CDE ring system of nakiterpiosin (1). Tetracyclic compound 25 may be a key intermediate in the total synthesis of 1. (c) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2007.05.174

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Language：Japanese   Publisher：The Society of Synthetic Organic Chemistry, Japan  

Brevetoxin B was isolated from the red tide organism Karenia brevis in 1981 as the first example of marine polycyclic ethers. This compound shows potent neurotoxicity, by binding to sodium channels, causing massive fish kills and human health problems. Since further biological studies are hampered by the limited availability from nature, chemical synthesis has been the sole realistic way to obtain sufficient amounts of brevetoxin B. Moreover, the huge molecular architecture is a particularly attractive target for synthetic chemists. In this account, we describe the highly convergent total synthesis of brevetoxin B based on our methodology, including intramolecular allylation and subsequent ring-closing metathesis.

DOI： 10.5059/yukigoseikyokaishi.65.430

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Other Link： https://jlc.jst.go.jp/DN/JALC/00293529271?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The octalin unit of symbioimine (1) has been synthesized stereoselectively via an intramolecular Diels-Alder reaction. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2006.07.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

An efficient synthesis of the A-G ring segment 2, a key intermediate for the total synthesis of brevetoxin B (1), was achieved in 37 steps and 5.0% overall yield. The intramolecular allylation of the O,S-acetal 22, prepared from the ABC ring segment 15 and the FG ring segment 17, was carried out using AgOTf as a Lewis acid to give the desired compound 23, predominantly. Ring-closing metathesis of 23 with the Grubbs catalyst 12 afforded the heptacyclic ether 25. Selective hydrogenation of the E ring olefin of 25 was performed by diimide reduction to afford 2.

DOI： 10.1021/jo0603025

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Language：Japanese   Publisher：The Society of Synthetic Organic Chemistry, Japan  

More than 20, 000 people suffer annually from ciguatera seafood poisoning in tropical and subtropical areas. The principal causative agents, ciguatoxin and its congeners CTX3C and 51-hydroxyCTX3C are extremely potent neurotoxins that bind to voltage-sensitive sodium channels. The extremely limited availability of these ciguatoxins has hampered the detailed biological studies and preparation of anti-ciguatoxin antibodies for detecting these toxins. Therefore the supply of these compounds by the chemical synthesis has been strongly demanded. Furthermore the unique structural features have attracted the attention of the synthetic chemists. This review has briefly focused on the synthetic studies of ciguatoxins in a convergent manner including a total synthesis.

DOI： 10.5059/yukigoseikyokaishi.64.418

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The convergent total synthesis of brevetoxin B (1) has been achieved. The intramolecular allylation of the 0,S-acetal 20, prepared from the alpha-chlorosulfide 17 and the alcohol 5, was carried out using AgOTf as a Lewis acid to give the diene 21, predominantly. Ring-closing metathesis of 21 with the Grubbs catalyst 23 afforded the hexacyclic ether 25 which was converted to the A-G ring segment 2 through several steps. The intramolecular allylation of the alpha-acetoxy ether 42, prepared from 2 and the J-K ring segment 3, followed by ring-closing metathesis provided the polycyclic ether framework 44. A series of reactions of 44, including oxidation of the A ring, deprotection of the silyl ethers, and selective oxidation of the resulting allylic alcohol, furnished 1.

DOI： 10.1021/ja051171c

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The convergent total syntheses of gambierol (1) and 16-epi-gambierol (2) have been achieved. The ABC and FGH ring segments 4 and 5 were prepared from known compounds 6 and 13, respectively, by linear manners. The fragments prepared were connected by our own synthetic strategy including the intramolecular allylation of alpha-acetoxy ether followed by ring-closing metathesis to furnish the octacyclic ether 3. The diiodoalkene 45, prepared from 3, was converted to the Z-iodoalkene 50 via a novel and stereoselective hydrogenolysis followed by deprotection. Construction of the triene side chain was performed by the modified Stille coupling of 50 with the Z-vinylic stannane 41 to afford 1. The similar transformations were carried out on the epimeric octacycle 34 to give 2, which showed no toxicity against mice at the concentration of 14 mg/kg.

DOI： 10.1021/ja036984k

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

DOI： 10.1021/ja028726d

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The reaction of the ketene acetal triflates 9a-e and a zinc homoenolate 10 in the presence of a catalytic amount of Pd(PPh3)(4) gave the enol ethers 11a-e in good yields. The products were converted to the corresponding cyclic ethers 14a and 14b by hydroboration and lactonization. The present methodology allowed us to synthesize the DE and GH ring segment of gambierol in a concise manner. Iterative syntheses of the polycyclic ethers 26 and 32 are also described.

DOI： 10.1021/jo025566f

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Stereocontrolled syntheses of the AB and EFGH ring systems of gambierol (1) are described. The two key intermediates 3 and 55, representing the AB and EFGH ring frameworks, were prepared from 2-deoxy-D-ribose via linear sequences. Brown's asymmetric allylboration and the intramolecular hetero-Michael reaction were successfully applied to the construction of the A ring moiety. Synthesis of the EFGH ring segment 55 was achieved by the SmI2 mediated reductive cyclization, constructing the EF ring bearing two 1,3-diaxial methyl groups, and the palladium catalyzed coupling of enol triflate and zinc bishomoenolate, making the GH ring moiety. Attempted convergent approaches toward the EFGH ring framework- are also described. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4020(02)00039-X

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The EFGH ring segment of gambierol was synthesized from 2-deoxy-D-ribose in 40 steps. The present synthesis includes a SmI2-mediated reductive cyclization and a Pd-catalyzed coupling of enot triflate with a zinc bis-homoenolate as key steps. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(01)01205-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Concise syntheses: of the DE and GH ring segments of gambierol (1) were achieved by the palladium-catalyzed coupling of ketene acetal triflates and a zinc homoenolate, followed by the hydroboration of the resulting cyclic enol ethers and subsequent lactonization. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(01)00824-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The J ring segment 2 of gambieric acid was synthesized stereoselectively by the coupling between the cyclic ether component 3 and the alkenyl iodide 4. The tetrahydropyran 3 was stereoselectively synthesized by the 6-endo-cyclization of a hydroxyepoxide prepared from deoxy-D-ribose. The side chain moiety 4 was prepared by the stereoselective hydrostannation of an internal alkyne. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(01)00530-5

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Language：Japanese   Publisher：Symposium on the chemistry of natural products  

Brevetoxin B (1), a potent neurotoxin, was isolated from the red tide organism Gymnodinium breve Davis in 1981. The unique structural features and biological activity of this molecule have attracted the attention of synthetic chemists. We have already reported the efficient method for the convergent synthesis of polycyclic ethers via the intramolecular allylation and subsequent ring-closing metathesis. Herein we report the convergent total synthesis of 1 based on our own methodology. The reaction of the bicyclic compound 9, prepared from the known compound 6, with the allylic silane 10 in the presence of TMSOTf gave the desired product 11, stereoselectively. The JK ring segment 3 was synthesized in 11 steps including one-carbon elongation from 11. Palladium-catalyzed coupling of the ketene acetal triflate 15 and the organozinc reagent 16 gave the enol ether 17, which was converted to the diene 22. The construction of the A ring via ring-closing metathesis afforded the ABC ring segment 4. The chlorosulfide 4 was treated with the alcohol 5 in the presence of AgOTf and DTBMP to give the O,S-acetal 24. Intramolecular allylation of 26 using AgOTf as a Lewis acid provided the desired product 27, stereoselectively. Chemoselective reduction of the olefinic moiety in the E ring of 29 was carried out under the condition of the diimide reduction to afford 30. The heptacyclic compound 30 was converted to the alcohol 2 in 6 steps including one-carbon elongation. The alcohol 2 and the carboxylic acid 3 were connected successfully by Yamaguchi conditions to give the ester 33. The construction of the polycyclic framework of 1 was performed via the intramolecular allylation and subsequent ring-closing metathesis to yield 38. After the TBS and TBDPS protecting groups were removed using HF・pyr, chemoselective oxidation of the allylic moiety with MnO_2 furnished brevetoxin B (1). The synthetic brevetoxin B exhibited spectroscopic data identical with those of natural brevetoxin B.

DOI： 10.24496/tennenyuki.47.0_325

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Language：Japanese   Publisher：Symposium on the chemistry of natural products  

Brevetoxin B (1), a potent neurotoxin was isolated from the red tide organism Gymnodinium breve Davis in 1981. The unique structural features and biological activity of this molecule have attracted the attention of synthetic chemists. We have already reported the efficient method for the convergent synthesis of polycyclic ethers via the intramolecular allylation and subsequent ring-closing metathesis. Herein we report the convergent synthesis of the polycyclic framework of 1 based on our own methodology. The reaction of the bicyclic compound 12, prepared from the known compound 9, with the allylic silane 13 in the presence of TMSOTf gave the desired product 14, stereoselectively. The JK ring segment 6 was synthesized in 11 steps including one-carbon elongation from 14. Palladium-catalyzed coupling of the ketene acetal triflate 22, prepared from the known compound 18, and the organozinc reagent 23 gave the enol ether 24, which was converted to the BC ring segment 7. The connection of 7 and the FG ring segment 8 followed by several transformations afforded the allylic stannane 29. The partial reduction of 29 with DIBALH followed by trapping of the resulting aluminum hemiacetal with acetic anhydride provided the acetoxy ether 30. However, the yield was very low. Alternatively, the chlorosulfide 31, prepared from 26, was treated with the alcohol 8 in the presence of AgOTf to provide the O,S-acetal 32. Cyclization of 33 using AgOTf as a Lewis acid gave the desired product 34, stereoselectively. The construction of the E ring and the A ring via ring-closing metathesis afforded the ABCDEFG ring segment 5. The alcohol 5 and the carboxylic acid 6 were connected successfully by Yamaguchi conditions to give the ester 41. The construction of the polycyclic framework of 1 was performed via the intramolecular allylation and subsequent ring-closing metathesis to yield 46. Completion of the total synthesis of 1 is currently under way.

DOI： 10.24496/tennenyuki.46.0_197

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Language：Japanese   Publisher：Symposium on the chemistry of natural products  

Gambierol (1) is a marine polycyclic ether isolated as a toxic constituent from cultured cells of the ciguatera causative dinoflagellate, Gambierdiscus toxicus. This compound shows toxicity against mice (LD_<50>, 50μg/kg), and the symptoms resemble those caused by ciguatoxins. The unique structural features have attracted the attention of synthetic chemist. We have already succeeded in the convergent synthesis of the CDEFG ring system (8) via the intramolecular allylation of the α-acetoxy ether 4 and subsequent ring-closing metathesis. Encouraged by this result, we started the total synthetic study of gambierol (1). Treatment of the cyclization precursor 15, prepared from the ABC ring segment 10 and FGH ring fragment 11, with MgBr_2・OEt_2 gave the desired product 9 and its C16 epimer 16 in 22% and 47% yield, respectively. The yield of 9 was improved by using monochloroacetoxy group as a leaving moiety. Thus, the reaction of 19 gave 9 and 16 in 30% and 48% yield, respectively. The diene 9 was subjected to ring-closing metathesis with 7 to give 20 in 84% yield. The octacyclic compound 20 was converted to 28 by several steps. We next examined the construction of the triene side chain. Although the Stille coupling of 29 and 30 gave the cross-coupling product 31 in an allowable yield (63%), the reaction was very slow (4 days). After unfruitful attempts, we succeeded in developping an efficient method for the stereoselective synthesis of Z-iodoolefin 33. Treatment of 32 with Zn-Cu and AcOH gave 33 as a single stereoisomer in 80% yield. As expected, the reaction of 33 and 30 was very fast. The triene 31 was obtained in 95% yield after 1.5h. Similaly, the iodoolefin 35, prepared from 28, was converted to the fully protected gambierol 36 in good yield. The final deprotection of 36 giving 1 is currently under way.

DOI： 10.24496/tennenyuki.44.0_151

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Language：Japanese   Publisher：Symposium on the chemistry of natural products  

A convergent synthesis of polycyclic ethers has been achieved by the intramolecular allylation of α-acetoxy ethers and subsequent ring-closing metathesis. The carboxylic acid 2 and alcohol 3 were connected by DCC coupling to give the ester 4 in 90% yield. After deprotection of the silyloxy group, the alcohol 5 was converted to the allylic stannane 8 via the mixed acetal 7 in good yield. The ester 8 was then subjected to the Rychnovsky protocol to give the α-acetoxy ether 9 as a mixture of diastereoisomers. The cyclization precursors 10-15 were prepared in a similar manner, and the results of the cyclization are summarized in Table 1. Treatment of 9 with 4 equiv of BF_3・OEt_2 gave a 70: 30 mixture of the cyclized products 16 and 17 in 79% yield (entry 1). Similarly, the cyclization of the substrates 10-15 proceeded stereoselectively to give the desired products in good yields (entries 2-7). We next examined the ring-closing metathesis of the products 18, 20, 22, 24, 25, and 27 (Table 2). Treatment of 18 with Grubbs catalyst 29 gave the tetracyclic ether 30 in 91% yield (entry 1). Similarly, the reactions of 20, 22, and 24 proceeded smoothly to afford the corresponding polycyclic ethers 31-33 in good yields (entries 2-4). Although the reactions of 25 and 27 with 29 were unsatisfactory, the use of the more active catalyst 34 provided the desired pentacyclic ethers 35 and 36 in high yield (entries 5 and 6). Based on these results, we have started the convergent synthesis of gambierol 1 and have synthesized the ABC and FGH ring segments, 48 and 60, from 2-deoxy-D-robose as shown in Schemes 2 and 3, respectively. Further studies toward the total synthesis of gambierol are now in progress in our laboratories.

DOI： 10.24496/tennenyuki.43.0_241

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Event date： 2023.9.13 - 2023.9.15

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